rs193920992

Positions:

• chr11-110624201-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001384657.1(ARHGAP20):​c.464T>C​(p.Val155Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARHGAP20 NM_001384657.1 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.92

Genes affected

ARHGAP20 (HGNC:18357): (Rho GTPase activating protein 20) The protein encoded by this gene is an activator of RHO-type GTPases, transducing a signal from RAP1 to RHO and impacting neurite outgrowth. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARHGAP20	NM_001384657.1	c.464T>C	p.Val155Ala	missense_variant	4/15	ENST00000683387.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARHGAP20	ENST00000683387.1	c.464T>C	p.Val155Ala	missense_variant	4/15		NM_001384657.1	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;.;.;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.89	D;D;.;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.74	D;D;D;D;D
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.8	M;.;.;.;.
MutationTaster	Benign	0.75	N;N;N;N;N;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D
REVEL	Uncertain	0.36
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.0040	D;D;D;D;D
Polyphen		1.0	D;D;.;.;.
Vest4		0.70
MutPred		0.47		Loss of sheet (P = 0.0142);.;.;.;.;
MVP		0.44
MPC		0.58
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.71
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs193920992; hg19: chr11-110494925; COSMIC: COSV52808662;